Variant 16-3089389-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032805.3(ZSCAN10):c.2045G>A(p.Arg682His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZSCAN10
NM_032805.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.459

Variant links:

Genes affected

ZSCAN10 (HGNC:12997): (zinc finger and SCAN domain containing 10) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated and regulation of transcription by RNA polymerase II. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29191884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN10	NM_032805.3 linkuse as main transcript	c.2045G>A	p.Arg682His	missense_variant	6/6	ENST00000576985.6	NP_116194.2	Q96SZ4I3L1J3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZSCAN10	ENST00000576985.6 linkuse as main transcript	c.2045G>A	p.Arg682His	missense_variant	6/6	5	NM_032805.3	ENSP00000458879.2	I3L1J3
ZSCAN10	ENST00000252463.6 linkuse as main transcript	c.1880G>A	p.Arg627His	missense_variant	5/5	1		ENSP00000252463.2	Q96SZ4-1
ZSCAN10	ENST00000538082.5 linkuse as main transcript	c.1634G>A	p.Arg545His	missense_variant	5/5	4		ENSP00000440047.2	Q96SZ4-3
ZSCAN10	ENST00000575108.5 linkuse as main transcript	c.863G>A	p.Arg288His	missense_variant	5/5	2		ENSP00000459520.1	Q96SZ4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450968

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722292

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.1880G>A (p.R627H) alteration is located in exon 5 (coding exon 5) of the ZSCAN10 gene. This alteration results from a G to A substitution at nucleotide position 1880, causing the arginine (R) at amino acid position 627 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;T;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.40

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.081

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.1

.;M;.;.

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-4.0

.;D;.;.

REVEL

Benign

0.25

Sift

Pathogenic

0.0

.;D;.;.

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.35

MutPred

0.53

.;Loss of methylation at R627 (P = 0.0188);.;.;

MVP

0.49

MPC

2.1

ClinPred

0.99

GERP RS

5.1

Varity_R

0.59

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over